Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to compare the toxicity, immunomodulatory changes, and antitumor efficacy of interleukin 2 (IL-2) and lymphokine activated killer (LAK) cell therapy with two durations of IL-2 infusion. Patients with progressive melanoma, non-Hodgkin's lymphoma, renal carcinoma, or colon carcinoma received IL-2 at 3 X 10(6) units/m2/day on days 1-5 and 13-17, either by bolus injection every 8 h (q8h) or by continuous i.v. (CIV) administration. Peripheral blood mononuclear cells were harvested by leukapheresis on days 8, 9, and 10, were incubated in vitro for 5 days for generation of LAK cells, and were infused on days 13, 14, and 15. The first 11 patients were treated with IL-2 q8h, and the subsequent 13 patients were treated by CIV infusion. Toxicity consisted primarily of fever, chills, emesis, diarrhea, weight gain, and edema but did not require intensive care unit support and did not differ significantly between treatment groups. IL-2-induced lymphocytosis on day 8 was higher with CIV than with q8h administration with a mean lymphocyte count/microliter of 5610 +/- 700 (SE) versus 3300 +/- 500. Immunomodulatory changes observed on days 8 and 20 were also greater with CIV IL-2 and included an increase in peripheral blood mononuclear cell IL-2 receptor expression as well as a marked rise in the number of Leu-11+ and Leu-19+ peripheral blood mononuclear cells. The total leukapheresis yield per patient and total number of LAK cells infused per patient were higher with CIV than q8h administration, with 49.8 +/- 4.9 X 10(9) versus 39.4 +/- 5.4 X 10(9) and 42.6 +/- 5.0 X 10(9) versus 34.0 +/- 5.4 X 10(9), respectively. The cells infused displayed phenotypic evidence of activation and exhibited marked lytic reactivity to Daudi, Raji, and HT-144 targets. One complete and one minimal response were observed in 2 of 8 patients with metastatic renal cell carcinoma who received CIV IL-2 and LAK cells. The results show that IL-2 is more biologically active by CIV than q8h administration, as demonstrated by greater rebound lymphocytosis, LAK cell yield, and in vivo immunostimulation.
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PMID:Influence of schedule of interleukin 2 administration on therapy with interleukin 2 and lymphokine activated killer cells. 278 43

The A6H mAb raised primarily against human renal cell carcinoma (RCC) has previously been shown to bind strongly to RCC, to some degree to colon carcinoma but only marginally to a variety of normal tissues. Immunohistochemical analysis or RCC tissues containing tumor-infiltrating lymphocytes revealed that A6H stained both tumor cells and lymphocytes. FACS analysis of human peripheral blood cells demonstrated that A6H stained both tumor cells and lymphocytes. FACS analysis of human peripheral blood cells demonstrated that A6H mAb stained 85-90% of both CD4+ and CD8+ T cells, but not granulocytes, monocytes, NK cells or B cells. Furthermore, 85-90% of naive and memory T helper cells were stained with A6H suggesting that the A6H mAb defines unique subsets within these T cell populations. Dual staining showed that A6H mAb bind to an antigen that is clearly distinct from other cell surface molecules on T cells, including CD28, CD29, CD26, CD44 and ICAM-2. A6H mAb binding induced a second signal in anti-CD3 mAb activated T cells, resulting in cell proliferation, IL-2 receptor expression and vigorous production of IFN-gamma and TNF, and production of minor amounts of IL-2. Immunoprecipitation with A6H mAb indicated a molecular weight of 120-140 kDa on both T cells and RCC. We suggest that the A6H mAb defines a unique T cell surface antigen which is involved in signal transduction and is expressed on subsets of human T cells. The co-expression of A6H on T cells and tumor cells suggests a possible function related to common properties of these cells.
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PMID:A novel co-stimulatory T cell antigen co-expressed on renal cell carcinoma. 749 50

Protein tyrosine phosphorylation is known to play key roles in lymphocyte signal transduction, and phosphotyrosine phosphatases (PTP) can act as both positive and negative regulators of these lymphocyte signals. We sought to examine the role of PTP further in these processes by characterizing the effects of bis(maltolato)-oxovanadium(IV) (BMLOV), previously known to be a nontoxic insulin mimetic agent in vivo. BMLOV was found to be a potent phosphotyrosine phosphatase inhibitor. BMLOV induced cellular tyrosine phosphorylation in B cells in a pattern similar to that observed following antigen receptor stimulation, whereas little tyrosine phosphorylation was induced in T cells. In B cells, BMLOV treatment resulted in tyrosine phosphorylation of Syk and phospholipase C gamma 2, while sIgM-induced signals were inhibited. By contrast, T cell receptor signals were moderately increased by BMLOV, and the cells displayed greater induction of IL-2 receptor without toxicity. The compound selectively induced apoptosis in B cell lymphoma and myeloid leukemia cell lines, but not in T cell leukemia or colon carcinoma cells. Interleukin-4 plus anti-CD40 antibody treatment of normal human peripheral B cells rescued the cells from BMLOV-induced death. These results suggest that phosphotyrosine phosphatase inhibitors can activate B cell signal pathways in a lineage-specific manner, resulting in desensitization of receptor-mediated signaling and induction of apoptosis.
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PMID:Lineage-specific induction of B cell apoptosis and altered signal transduction by the phosphotyrosine phosphatase inhibitor bis(maltolato)oxovanadium(IV). 765 67

Genetically engineered tumor cells secreting immunostimulatory molecules could facilitate the obtention of a vaccination against tumor antigens. To test this approach, we transfected genes encoding for rat and mouse IL-2 into PROb cells. These cells originate from a dimethylhydrazine induced colon carcinoma of BD IX rats. We observed an inhibition of the in vivo tumor growth directly proportional to the IL-2 secretion. An immunohistochemical analysis revealed that the tumors were infiltrated by leucocytes expressing the IL-2 receptor, suggesting their activation within the tumor. A strong delay of tumor growth was observed in rats challenged with PROb cells after a previous rejection of IL-2 secreting cells. Yet two rats out of six were completely protected. This protection is specific since rejection of PROb-IL-2 does not confer protection towards the syngeneic glioma A15A5. In addition, we could show by depletion experiments that NK/LAK, CD8, and CD4 lymphocytes were involved in the rejection of cells secreting large amounts of IL-2. Macrophages appear to be involved in the rejection process too, but also in the induction of an immune memory. Vaccination experiments using irradiated PROb IL-2 cells were performed. Only a partial protection towards a challenge with parental PROb cells could be obtained, also depending on the amount of secreted IL-2: the best protection being obtained after vaccination with cells synthesizing a small amount of IL-2. However, this protection was not superior to that obtained by coinjection of irradiated PROb cells and BCG.
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PMID:[Vaccination with genetically modified IL-2 secreting cells in a rat model of colonic carcinoma]. 869 24